The prime objective of this research proposal is to develop potent and selective beta-adrenoceptor stimulants which are structurally related to trimetoquinol. The project includes the synthesis and pharmacological evaluation of trimetoquinol derivatives. The trimetoquinol analogs will be studied for the relative degree of adrenoceptor activity in isolated bronchial muscle, heart muscle, rat adipocytes, and skeletal muscle preparations. Assessment of alpha-adrenoceptor activity for trimetoquinol analogs will be tested in isolated aortic strip preparations. Trimetoquinol analogs which exhibit significant biological activity and possess asymmetric centers will be resolved into enantiomers and reexamined for stereoselective interaction with adrenoceptor systems. We also plan to examine the mechanism of adrenoceptor (agonist or antagonist) action of selected trimetoquinol derivatives by an elucidation of their qualitative and quantitative interacion with (a) adenylate and/or guanylate cyclase, and (b) cyclic nucleotide phosphodiesterase enzyme systems. Particular emphasis will be placed upon the quantitative relationship between changes in tissue levels of cyclic nucleotides, such as cyclic 3',5'-adenosine monophosphate, and drug-induced effects on these enzyme systems. This project will provide basic stereochemical information on the mode of pharmacological action exhibited by trimetoquinol derivatives in adrenoceptor systems which we associated with the maintenance of normal cardiopulmonary function.